RobI in U.S. Pat. No. 5,508,272 discloses compounds of the formula ##STR1##
wherein A is ##STR2##
as possessing neutral endopeptidase and angiotensin converting enzyme inhibition activity. Among these compounds is [4S-[4.alpha.(R*), 7.alpha., 10a.beta.]]-octahydro-4-[(2-mercapto-1 -oxo-3-phenylpropyl)amino]-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxy lic acid which is currently undergoing clinical evaluation. This compound is reported herein as (1)
RobI discloses that the amino lactam portion of (1), i.e., the intermediate ##STR3##
can be prepared by coupling (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester with the N-protected amino acid ##STR4##
wherein P.sub.1 is an amino protecting group and P.sub.2 is a sulfur protecting group to give the dipeptide of the formula ##STR5##
Removal of the P.sub.2 protecting group, followed by acid catalyzed cyclization, and removal of the P.sub.1 protecting group gives [4S-(4.alpha., 7.alpha., 10a.beta.)]-octahydro-4-amino-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carb oxylic acid, methyl ester.
RobI discloses preparing (S)-2-amino-6,6-dialkoxyhexanoic acid, alkyl ester, such as (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester, by converting N-protected L-.epsilon.-hydroxynorleucine to its methyl ester, oxidizing to a corresponding aldehyde, such as of the formula ##STR6##
then reacting with trimethyl orthoformate in the presence of a strong acid catalyst, and removing the P.sub.3 protecting group.